title: New phosphatidylinositol 3-kinase inhibitors for cancer.
abstract: BACKGROUND
  Cancer treatment is moving away from conventional cytotoxic drugs and towards agents that target specific proteins important to cancer development or survival. The PI3K signaling axis is an important pathway involved in myriad human malignancies. Inhibition of this axis is a promising therapeutic approach for several cancers.
  
  
  METHODS
  This article reviews current literature and recent conference proceedings to analyze the rationale for targeting PI3K and its downstream effectors in cancer. Preclinical and clinical results of several PI3K and PI3K--mammalian target of rapamycin (mTOR) inhibitors in early clinical trials, as single agents and in combination with other drugs, are discussed. Thus far, clinical results have been mixed.
  
  
  CONCLUSIONS
  The clinical utility of PI3K and PI3K--mTOR inhibitors will depend on appropriate selection of patients. Mutations in the PI3K pathway may predict sensitivity to PI3K inhibition but they are not reliable biomarkers at this point. Efforts to define predictive biomarkers will probably be the key to finding therapeutic uses for this novel class of anticancer agents.
authors.affiliation: University of Colorado Comprehensive Cancer Center, Aurora, CO 80045, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bowles
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D058539:Phosphatidylinositol 3-Kinase; D058570:TOR Serine-Threonine Kinases